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  Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 3  |  Page : 448-451
 

Epidemiology and resistance pattern of bacterial isolates among cancer patients in a Tertiary Care Oncology Centre in North India


1 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India
2 Department of Lab Medicine, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India

Date of Web Publication24-Feb-2017

Correspondence Address:
U Batra
Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.200647

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 » Abstract 

OBJECTIVES: To examine the epidemiology of microbiologically documented bacterial infection and the resistance pattern, among cancer patients undergoing treatment at RGCIRC, Delhi. DESIGN AND SETTING: Retrospective observational study in which culture reports obtained over 1 year in 2013, were analyzed. RESULTS: 13329 cultures were obtained over 1 year in 2013 and were analyzed. 23.6 % samples showed positive culture with majority being gram negative isolates (67.9 %). E. coli was the commonest gram negative isolate (49.4%) followed by klebsella (29.7%) and Staph. aureus was the commonest gram positive isolate. There was high incidence of ESBL in blood and urine (87.2% & 88.5%) and BLBLI were also high (78% & 83.9%). Carbapenem resistance was comparatively low (10%) and colistin sensitivity was quiet high (> 95%). CONCLUSIONS: Prevalence of MRSA and VRE in our institute is very less, whereas prevalence of ESBLs and BLBLI isolates amongst gram negative infections is around 80%. Gram negative isolates had poor sensitivity to cephalosporins and fluoroquinolones.


Keywords: Epidemiology of bacterial isolates, infections in cancer patients, resistance pattern of bacterial isolates


How to cite this article:
Batra U, Goyal P, Jain P, Upadhyay A, Sachdeva N, Agarwal M, Bhurani D, Talwar V, Gupta S, Doval D. Epidemiology and resistance pattern of bacterial isolates among cancer patients in a Tertiary Care Oncology Centre in North India. Indian J Cancer 2016;53:448-51

How to cite this URL:
Batra U, Goyal P, Jain P, Upadhyay A, Sachdeva N, Agarwal M, Bhurani D, Talwar V, Gupta S, Doval D. Epidemiology and resistance pattern of bacterial isolates among cancer patients in a Tertiary Care Oncology Centre in North India. Indian J Cancer [serial online] 2016 [cited 2017 Jul 21];53:448-51. Available from: http://www.indianjcancer.com/text.asp?2016/53/3/448/200647



 » Introduction Top


Infections remain a major cause of morbidity and mortality in cancer patients. They also cause suboptimal delivery of chemotherapy which leads to poor treatment outcome, adds to cost of management, and contribute to increased morbidity. Algorithmic approaches for prophylaxis and management for fever and neutropenia have been established by various international organization such as Infectious Diseases Society of America (IDSA)[1] and European Conference on Infections in Leukemia [2] yet the multidrug resistant bugs are difficult to manage and pose a difficult challenge as the international guidelines does not hold good in different geographical areas and communities. Appropriate empiric antibiotic therapy on the basis of local sensitivity pattern in that area is, therefore, critical to a successful outcome. Hence, the current study was planned with the objective of studying the epidemiology of microbiologically documented bacterial infection and the resistance pattern, among cancer patients undergoing treatment at our institute.


 » Materials and Methods Top


This is a single institutional study carried out in the Departments of Hematology-oncology and Microbiology of a Tertiary Care Cancer Centre in North Delhi. The study population included all patients with various malignancies undergoing treatment in our hospital including outpatient on follow-up who had bacterial cultures sent for various reasons in 1 year, between January 2013 and December 2013. All the 13,329 culture reports during the study period were retrieved from the database of the Department of Microbiology. The demographic details and culture reports for patients with positive isolates were retrieved from their medical records.

These samples for culture from the relevant site were received from all the patients who had a fever or any other clinical focus of infection before starting empirical antibiotics or in between if the fever was not responding to the therapy. The time of sample collection was determined by the clinical status of the patient and physician's advice. Organisms were isolated from blood, urine, stool, pus swab, wound swab, respiratory secretions, body fluid specimens, etc., of the patients. All specimens were cultured on different media using standard bacteriological procedures. Blood cultures were routinely collected in aerobic and fungal media and incubated using the BacT/ALERT 3D system (Biomeriux, USA). The bacterial isolates were identified manually and by an automated system (Mini API, Biomeriux). In vitro sensitivity, patterns were studied by Kirby–Bauer disc diffusion method and by using Mini API according to Clinical Laboratory Standard Institute guidelines.

Gram-negative organisms isolated from any sample were subjected to an automated system for sensitivity and identification if required. For blood samples, stained, Gram-negative, automated identification, and sensitivity was done. The Gram-positive isolates were subjected to a manual method for identification and sensitivity. Whereas methicillin-resistant Staphylococcus aureus (MRSA) identification was done using – Hi Chrome MeReSA agar.

ESBL was interpreted as present whenever the inhibition zone around the disk containing clavulanate was at least 5 mm larger than that of the disk containing the same cephalosporin but without clavulanate. Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 strains were used as controls. An analysis of microbiological spectrum and the antibiotic sensitivity pattern of the bacterial isolates were performed. Clinical outcome of resistant isolates was analyzed.

Categorical variables were described as frequency and percentage, and continuous variables as median and interquartile range. For continuous variables, mean values were compared using two sample t-tests for independent samples. Differences in proportions were compared using a Chi-square test or Fisher's exact test, as appropriate. P value of <0.05 was considered statistically significant. The analyses were performed using SPSS ver­sion 16.0 for Windows (SPSS Inc., Chicago, USA).


 » Results Top


It is a retrospective analysis of the epidemiology of microbiological isolates in patients with malignancies over a period of 1 year, January 2013 to December 2014. The source of specimen was as outlined in [Table 1]. During the study period, a total of 13,329 culture samples were sent of which 5593 (41.9%), 4058 (30.5%), and 3678 (27.6%) were samples from blood, urine, and other sites, respectively. Of the total samples, 23.6% (3144) showed positive culture. In this culture, positive samples 67.9% (2136/3144) were Gram-negative and 15.9% (500/3144) was Gram-positive, 16.2% (508/3144) being fungal. After excluding fungal, there were 2636 positive bacterial cultures [Table 2].
Table 1: Culture sample distribution

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Table 2: Distribution of positive isolates

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Probability of detection of microbiological culture positive isolate from blood stream was 12% (676/5593) and 19.5% (792/4058) from urine samples and 31.8% (1168/3678) from other sites. Probability of Gram-positive isolates from blood stream, urine, and other specimen was 3.82% (214/5593), 2.24% (91/4058), and 5.3% (195/3678), respectively. Probability of Gram-negative isolates from blood, urine, and other sites constituted 8.2% (462/5593), 17.27% (701/4058), and 26.45% (973/3678), respectively [Table 3].
Table 3: Probability of culture positivity

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Of all Gram-negative cultures, E. coli was the most common Gram-negative isolate 49.4% (1056/2136) followed by Klebsiella 29.7% (635/2136) and Pseudomonas 17.7% (379/2136). Of all Gram-positive isolates, 68.8% (344/500) were Staphylococcus aureus and 31.2% (156/500) were Enterococcus.

In blood, out of 676 positive samples, 462 (68.3%) were Gram-negative, and 214 (31.7%) were Gram-positive. Out of 462 Gram-negative isolates in blood, E. coli was again the most common Gram-negative isolate 52.6% (243/462) followed by Klebsiella 35.1% (162/462) and Pseudomonas 11% (51/462). Out of 214 Gram-positive isolates, S. aureus was the most common Gram-positive isolate 79% (169/214) followed by Enterococcus 21% (45/214).

In urine, out of 792 positive samples, 701 (88.5%) were Gram-negative, and 91 (11.5%) were Gram-positive. Out of 701 Gram-negative isolates, E. coli was the most common Gram-negative isolate 64.6% (453/701) followed by Klebsiella 19.7% (138/701) and Pseudomonas 13.3% (93/701). Out of 91 Gram-positive isolates, S. aureus was detected in 7.7% (7/91) and Enterococcus in 92.3% (84/91).

In all other, out of 1168 positive samples, 83.3% (973/1168) were Gram-negative, and 16.7% (195/1168) were Gram-positive. Out of 973 Gram-negative isolates, E. coli was the most common Gram-negative isolate 37% (360/973) followed by Klebsiella 34.4% (335/973) and Pseudomonas 24.1% (235/973). Out of 91 Gram-positive isolates, S. aureus was detected in 86.1% (168/195) and Enterococcus in 13.9% (27/195) [Table 4].
Table 4: Distribution of Micro-organisms in various culture groups

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Among 1056 total isolates of E. coli, 243 were from blood, and there resistance pattern is worrisome as the presence of ESBL in 212 (87.2%), BLBLI in 190 (78%), and carbapenem resistance in 24 (10%) isolates. 78% of these isolates were resistant to quinolones and aminoglycosides. 42.9% (453/1056) isolates of E. coli were from urine, and there resistance pattern is the presence of ESBL in 401 (88.5%), BLBLI in 380 (83.9%), and carbapenem resistance in 50 (11.3%) isolates. 81% (367/453) and 75.9% (344/453) of these isolates were resistant to quinolones and aminoglycosides, respectively.

Among the 635 isolates of Klebsiella sp., 25.5% (162/635) were from blood and the resistance identical to E. coli as presence of ESBL in 77% (125/162) samples, BLBLI in 72.8% (118/162), carbapenem resistance in 50% (81/162) isolates and for quinolones and aminoglycosides it was 87.6% and 69.1%, respectively. 21.7% (138/635) were from urine and the resistance pattern is presence of ESBL in 72.4% (100/138) samples, BLBLI in 68.1% (94/138), carbapenem resistance in 44.2% (60/138) isolates and for quinolones and aminoglycosides it was 81.2% (112/138) and 65.2% (90/138), respectively.

Among the 379 isolates of Pseudomonas, 13.4% (51/379) were from blood. The resistance pattern revealed presence of ESBL in 54% (28/51), BLBLI in 94% (48/51), while carbapenem resistance was 94% (48/51) and for quinolones and aminoglycosides it was 51% and 5.9% respectively. 24.5% (93/379) were from blood. The resistance pattern revealed presence of ESBL in 48.4% (45/93), BLBLI in 94.6% (88/93), while carbapenem resistance was 93.5% (87/93) and for quinolones and aminoglycosides it was 48.4% (45/93) and 16.1% (15/93), respectively.

In isolates from blood, colistin showed the sensitivity of 97.7%, 98.9% and 94.7% in E. coli, Klebsiella and Pseudomonas, respectively. In isolates from urine, colistin showed the sensitivity of 98.3%, 96.1%, and 90% in E. coli, Klebsiella and Pseudomonas, respectively.

Among the 344 total isolates of S. aureus, 169 (49.1%) were from blood and MRSA was detected in 3/169 (1.8%), 175 (50.9%) were from other sites MRSA was seen in 2/175 (1.1%) [Table 5].
Table 5: Resistance pattern of gram-positive isolates

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Among the 156 total isolates of Enterococcus, 45 (28.8%) were from blood and vancomycin-resistant Enterococcus (VRE) was detected in 2/45 (4.4%), 111 (71.2%) were from other sites and VRE was detected in 2/111 (1.8%) [Table 5].


 » Discussion Top


Our study population comprised of hematological and solid cancer patients which represents a vulnerable population because of alterations in host defense mechanisms against infection and repeated hospital admissions. Moreover, these patients are coming from distant places and there infection pattern may have been altered by the local bacterial isolates and there sensitivity pattern. This also may be related to the underlying illness, cytotoxic therapy, and frequent presence of indwelling catheters, stents, and prosthesis. In this setting, while managing the cancer with cytotoxic therapy, the main limiting factor is dealing with various infections which at times become more life-threatening than the disease itself unless dealt timely with appropriately drugs. Algorithmic approaches to fever have been recommended by international bodies such as IDSA 1 but the local prevalence of various organisms and their sensitivity varies with the hospital and geographical area. First-hour presumptive treatment with appropriate antibiotics is the major factor which decides the final outcome in these patients for which updated audit and analysis of the microbiological isolates and their sensitivity pattern is the key to manage these patients.

In the present study, blood culture positivity rate was 12.1% (676/5593) over 1 year. Identification of the causative microorganisms of infection from blood has been previously reported to be higher (22–39%).[3],[4] This low prevalence may be due to a policy of sending a set of two samples at times, one from indwelling venous catheter and other from the peripheral line at the time of onset of fever and repeat cultures while patients being on antibiotics. Yield from other sites and urine culture was relatively higher as it was ordered usually in symptomatic patients.

In the present study, of all isolates from blood 63.2% (462/737) were Gram-negative and 29.3% (214/737) were Gram-positive. This is in accordance with many studies published from the developing countries like by Prabhash et al.[3] from Mumbai (68.1%) and Karanwal et al. (78%) from Ahmedabad.[4] However, the relatively low prevalence of Gram-positive isolates may also be attributed to the policy of not using prophylactic antibiotics, better prevention of Gram-positive infection owing to trained and experienced line care staff. Furthermore, locally prevalent resistant Gram-negative bacterial flora and relatively sensitive Gram-positive strains might have contributed to this. S. aureus was the most common Gram-positive isolate whereas the most common Gram-negative isolates were E. coli followed by Klebsiella pneumoniae and P. aeruginosa. A similar observation was made by Saghir et al. in his study done in 2000–2001 at 33 oncology centers, clinics, and hospitals in North America.[5] These findings depict that the pattern of isolates in immunocompromised patients are variable in different parts of the world with Gram-negative more common in developing countries.

In our study, the prevalence of MRSA and VRE is very less (<10%) which is quite less compared to other studies.[4],[6] This could be due to the hospital policy of rotating antibiotic usage and reserving drugs such as vancomycin for positive or high probability cultures than using them empirically and policy of isolating the MRSA and VRE infected patients.

In the present study, we had 80% prevalence of ESBLs and BLBLI isolates among Gram-negative infections from various sites as has been seen in other studies as well.[7],[8] Gram-negative isolates had poor sensitivity to cephalosporins and fluoroquinolones, and a similar observation was made by Prabhash et al.[3] and Saghir et al.[5]

Polymicrobial resistance to fluoroquinolones and aminoglycosides in ESBL and BLBLI isolates in such patients lead to choose costly antibiotics such as carbapenem and colistin but then prolonged usage may exhaust these antibiotics as well, carbapenem resistance can obviously see in half of the Klebsiella strains. Antibiotics discovery is lagging far behind the resistance pattern of these smart organisms further emphasizing on the smart policy driven usage of our present armatarium [Table 6].
Table 6: Resistance pattern of gram-negative isolates

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Our study has certain limitations. First, it was performed in a single institution, which may not reflect the epidemiology of different centers and/or different geographic areas. Second, being a retrospect study we did not have the details of the timing of samples sent whether before or on antibiotics, underlying disease - hematological or solid malignancy and previous antibiotic exposure as they may have different epidemiologic, clinical characteristics, and microbial pattern.

There is a dire need to conduct a yearly analysis of the microbial pattern with a prospective to further improvise on our decision making in different clinical scenarios. This alarmingly high prevalence of resistant organisms highlights the importance of formulating and revising such local microbiological analysis and also need to formulate certain institutional protocols to stop excessive usage of higher antibiotics.

 
 » References Top

1.
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011;52:e56-93.  Back to cited text no. 1
    
2.
Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: Summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013;98:1826-35.  Back to cited text no. 2
    
3.
Prabhash K, Medhekar A, Ghadyalpatil N, Noronha V, Biswas S, Kurkure P, et al. Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern. Indian J Cancer 2010;47:184-8.  Back to cited text no. 3
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4.
Karanwal AB, Parikh BJ, Goswami P, Panchal HP, Parekh BB, Patel KB. Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center. Indian J Med Paediatr Oncol 2013;34:85-8.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.
Saghir S, Faiz M, Saleem M, Younus A, Aziz H. Characterization and anti-microbial susceptibility of gram-negative bacteria isolated from bloodstream infections of cancer patients on chemotherapy in Pakistan. Indian J Med Microbiol 2009;27:341-7.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
6.
Mutnick AH, Kirby JT, Jones RN; CANCER Study Group. CANCER resistance surveillance program: Initial results from hematology-oncology centers in North America. Chemotherapy alliance for neutropenics and the control of emerging resistance. Ann Pharmacother 2003;37:47-56.  Back to cited text no. 6
    
7.
Ghosh I, Raina V, Kumar L, Sharma A, Bakhshi S, Thulkar S, et al. Profile of infections and outcome in high-risk febrile neutropenia: Experience from a tertiary care cancer center in India. Med Oncol 2012;29:1354-60.  Back to cited text no. 7
    
8.
Lakshmaiah KC, Abhayakumar SM, Shetty R, Loknath D, Jayashree RS, Govindbabu K. Management of febrile neutropenia in solid organ malignancies following chemotherapy. J Cancer Res Ther 2014;10:540-3.  Back to cited text no. 8
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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